The objective of this project is to develop new technology for the detection and analysis of biomolecules based on novel photocleavable linkers (PC-linkers), photocleavable-markers (PC-markers) and matrix assisted laser desorption ionization mass spectrometry (MALDI-MS). PC- linkers facilitate the capture of biomolecules on surfaces and subsequent photorelease for analysis by MALDI-MS. PC-markers facilitate simultaneous identification of different biomolecules in a complex mixture by MALDI-MS. During Phase I, AmberGen, Inc. has begun development of a range of proprietary reagents and methodologies for incorporating PC-linkers and PC-markers into oligonucleotides and proteins. Examples of reagents developed and evaluated include PC- aminotag-phosphoramidites for 5'-end labeling of oligonucleotides during solid-support synthesis and PC-nucleotides which can be incorporated enzymatically into oligonucleotides. A proprietary method for the synthesis of oligonucleotide probes with photocleavable peptide mass markers (PC-SNAPs) has been developed based on the use of a DNA/RNA solid phase synthesizer. Peptide mass markers have many attractive features which include a large set of unique resolvable masses, stability to fragmentation and automated synthesis. During Phase II, this new technology will be further developed and used in a variety of applications including the analysis of PCR products, rapid sequencing of DNA, and molecular diagnosis based on DNA and protein analysis. PROPOSED COMMERCIAL APPLICATION: The development of photocleavable linkers and photocleavable markers for mass spectrometry will have widespread commercial applications in many areas of biotechnology involving the detection and analysis of biomolecules. Products will include photocleavable reagents, photocleavable markers, photocleavable surface arrays for mass spectrometry, and diagnostic assays at both the DNA and protein level for a variety of health care applications.